Published On March 23, 2020
VACCINES HAVE HISTORICALLY TAKEN DECADES TO DEVELOP. The urgency imposed by COVID-19 is clear and that push may be helped by two factors: advances in vaccine technology, and insights from working on other diseases.
Both of these factors could boost an effort coordinated by the Ragon Institute of MGH, MIT and Harvard, one of nearly three dozen COVID-19 vaccine projects currently under way around the world. Since the Ragon Institute’s inception in 2009, its researchers have concentrated on HIV/AIDS, puzzling through the inscrutable virus for hints of how to build an effective vaccine. Dan Barouch, an infectious disease specialist at the Ragon Institute and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, has been central to those efforts, and his team has switched its focus to COVID-19 since early January.
Q: How are your insights on HIV vaccine development translating to COVID-19?
A: This is not the first time we have applied our work toward an acute viral epidemic. In 2016 we were able to rapidly develop vaccine candidates for Zika, and one of those, in later clinical trials, showed remarkable potency in humans, which is what you want.
On Friday, January 10, of this year, the sequence of the novel coronavirus was released by Chinese researchers. We were immediately concerned that this virus had global pandemic potential, so we started working on it right away. That same night, our team started analyzing the sequence, and we worked over the weekend. By Monday, January 13, we had designed COVID-19 vaccine immunogens—the part of the vaccine that triggers the body’s immune response.
Since then, we have put the key immunogen, called the spike protein, in two relatively new delivery vehicles: DNA vaccines and recombinant adenovirus vectors, which deliver the immunogen via a harmless common cold virus. These are the same platforms that we used for Zika. We’re already evaluating these vaccine candidates in mice, ferrets and rhesus monkeys. On March 13, we announced that Johnson & Johnson will be working with our group on clinical development of the adenovirus vaccine.
Q: What makes the adenovirus vaccine the most promising option?
A: Adenovirus vaccine vectors have a record for safety and the ability to promote robust immune responses in humans. A single dose of an adenovirus vector can generate antibodies that last a long time. Most importantly—and this is very important for a COVID-19 vaccine—adenovirus vectors can be manufactured at large scale. Johnson & Johnson produced two million doses of the Ad26 Ebola adenovirus vaccine. The know-how for manufacturing large numbers of doses for this kind of vaccine already exists.
Q: What is a realistic timeline for a vaccine?
A: It is impossible to predict with certainty. People in my lab have been working on this project every day since January 10. I said to my team, “Let’s make a vaccine as fast as possible—and hope that the epidemic subsides and that we won’t need it.”
We hope this vaccine will be in a clinical trial this fall. But starting a phase one study is very different than having millions of doses available to the general public. We should be clear about that when we talk about vaccines. There is no way right now to predict the timeline for having a vaccine widely available. We also need multiple vaccine candidates to move into clinical development as soon as possible, because at this point we don’t know which one will be the safest, most effective and easiest to deploy.
It will take at least a year to have a vaccine widely available, and if that occurs, it will be the fastest vaccine development in history.
Q: A lot of vaccine projects are in motion. How does your work fit in with the others?
A: According to the World Health Organization, there are approximately three dozen ongoing vaccine efforts for COVID-19. They are largely clustered into different ways to deliver a vaccine, which include DNA vaccines, RNA vaccines, protein vaccines and recombinant vector-based vaccines, as well as the inactivated virus approach.
Not all of these vaccines will make it into large-scale clinical trials, even if first-stage clinical studies look good. Thus, some level of redundancy is strategically a very good thing.
In Seattle, they have started testing an RNA vaccine in human volunteers. RNA vaccines are a promising new vaccine technology, so we’re hoping those results will look very good and that vaccine candidate moves forward quickly. But so far RNA vaccines have never been produced at a scale of hundreds of millions of doses.
Q: How much information sharing is happening between these different efforts?
A: There is a lot of collaboration and information sharing, because vaccine development is intrinsically collaborative. There’s collaboration at the level of data before these products go into animals or humans. And there’s collaboration in terms of how we are planning to test our products in clinical trials.
Q: What factors could speed up or slow down the timeline?
A: What will speed up the timeline is to manufacture the vaccine upfront at larger scales. That lets us move forward with more tests quickly in the event of a success. One thing that might slow down the vaccine is that there’s a theoretical concern from some preclinical data many years ago about a problem known as antibody-dependent enhancement of disease—in which the antibodies you produce actually worsen the infection. This has not yet been seen for COVID-19 vaccines or for even SARS vaccines in humans, but it has been seen in humans with vaccines for RSV, or respiratory syncytial virus. That would be a wrinkle that would slow us down.
Q: What do we know at this point about how quickly this virus mutates and what implications will that have for developing a vaccine?
A: From the HIV field, we know firsthand the challenges of how virus mutation and virus variability can impact a vaccine. So far, for the coronavirus, most of the spike protein sequences are very similar. There is a mutation that has emerged in Europe, but so far, virus evolution in the key vaccine targets has been slow. So we remain cautiously optimistic, but we’ll continue to track the evolution of this virus.
Q: A major study from the Imperial College of London predicted that the world will divide into two camps by the end of the year: developed countries still undergoing suppression and waiting for vaccines, and developing countries emerging from short epidemics with herd immunity—their natural form of protection resulting from already having had the infection. What do you think about this scenario?
A: It’s very difficult to predict the trajectory of the epidemic. Neither the explosive epidemic nor the rapid decline in cases in China was predicted. The rate at which epidemics in Europe and the United States might peak is also not known. So it’s very difficult to predict what’s going to happen.
Q: Will it take a vaccine to end the epidemic?
A: We don’t know for sure. We know that the virus has the potential for explosive spread and also that it can be spread by asymptomatic individuals. Right now, since we don’t have a vaccine, the only tools we have are the epidemiologic ones, namely social distancing, to slow the spread of the virus in populations. That is absolutely critical for every single person right now. It’s possible that through public health measures, the epidemic might subside by itself before vaccines are available. It’s also possible the epidemic will not subside fully or if it does, it might recur, in which case a vaccine might be important for helping to bring the epidemic to a durable end. That assumes that a vaccine will be successfully developed and that it will be safe and effective.
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